This invention relates to an immunosuppressant comprising Glucopyranose derivatives of the formula (I): 
wherein all symbols are as hereinafter defined, or non-toxic salts thereof as active ingredient.
An immunoreaction is a system to protect the organism from a foreign matter as a protective reaction. However, sometimes an injury is happened for an organism by an immunoreaction that naturally plays to protect an organism. As diseases caused by the above injury, there are allergic diseases and autoimmune disease.
Recently, allergic diseases, e.g. allergic asthma, atopic dermatitis containing urticaria, allergic rhinitis, allergic conjunctivitis, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis, are increased. It is consider that these diseases are caused by peculiarity IgE antibody against an antigen in blood. Then there is lot of case that interleukin 5 (IL-5) and eosinophils are increased in a chronic condition. And the increase is also showed in a mild case. Allergic bronchopulmonary aspergillosis is asthma as a spore of aspergillosis is an antigen, and it possesses a peculiarity IgE antibody. And it showed an acute cutireaction. The treatment is same method with generally bronchial asthma [Saishin Naikagaku Taikei 61 (Nakayama): pneumoniaxc2x7interstitial pneumonia, 157-158 (1992); Saishin Naikagaku Taikei 62 (Nakayama): bronchial asthmaxc2x7allergic asthma, 81-91 (1992)].
One of the allergic diseases excepted the above, with the proviso that a part is overlapped, is hyper IgE syndrome containing purulence, low of wandering of leukocyte and atopic dermatitis. It is showed an abnormal mechanism of neutrophil. It is characteristic to show hyper IgE in blood, an atopic dermatitis like eczema and an infection by recurrent yellow staphylococcosis [Tadamichi MASU et al., hyper IgE syndrome, new allergic dermatitis (editor is Hikotaro Yoshida), 143 (1991)].
Besides, PIE syndrome, pulmonary eosinophilia, e.g. Loeffler syndrome, chronic eosinophilic pneumonia, acute eosinophilic pneumonia, tropical eosinophilia, allergic granulomatous angiitis, allergic bronchopulmonary mycosis, eosinophilia; and eosinophilic fasciitis accompanying increases of IL-5 and IgE antibody in a serum are known as allergic diseases [Enright T. et al., xe2x80x9cPulmonary eosinophilic syndromexe2x80x9d Ann. Allergy, 62, 277 (1989), and Saishin naikagaku taikei 24 (Nakayama): collagen diseases, similarity diseases thereof, 112-116 (1992)].
Allergic diseases that caused by abnormal enhancement of immunity, such as an increase of IgE antibody that is peculiarity against an antigen, increases of IL-5 and eosinophils, are increased.
General treatments of allergic diseases are carried out to prevent an inhalation or take of antigen, e.g. cedar pollens, acarid, spore of aspergillosis and some foods; into body, and to use medicines, e.g. anti-histamine, steroid.
However, a fundamentally treatment is difficult. As mentioned above, if abnormal enhancement of immunity, e.g. increases of IgE antibody that is peculiarity against an antigen, IL-5 and eosinophils, are main reasons of allergic diseases, use of medicines possessed an inhibitory activity of enhancement of immunity has a possibility to be a fundamentally treatment of allergic diseases.
On the other hand, T cells also play an important roll on an immunoreaction. An activated T cells product various cytokines, such as interleukin 4 (IL-4), interleukin 2 (IL-2), interferon xcex3 (IFN-xcex3), and assist an activity of immunoreaction.
The other way, a production of these cytokines also causes allergic diseases and autoimmune disease. IL-4 is related mainly to an activity of B cells stimulated by antigen, and it promotes a production of IgE. IL-2 has an increasing activity for T cells and B cells stimulated by antigen. IFN-xcex3 causes an inducement of differentiates of killer T cells and an activity of macrophage.
Accordingly, it is expected to improve allergic diseases, such as diseases described hereinbefore and autoimmune disease, e.g. chronic rheumatism, psoriasis, multiple sclerosis, and ulcerative colitis, which related to immunoreaction.
Glucopyranose derivatives of the present invention of the formula (I) 
wherein all symbols are as hereinafter defined; or non-toxic salts thereof are disclosed to have an activity of lipid A like, and an activation of immune, e.g. activation of macrophage, a blastogenesis action of B cells, an product action of non-peculiar antibody, an activation of cell-mediated immunity; antineoplastic activity, e.g. an activation of inducement of interferon, an activation of product of interleukin, an activation of inducement of TNF; in Japanese Kokoku-koho Hei 4-74359 (EP 0226381) or Japanese Kokai-koho Hei 1-52793 (EP 0288888).
Besides, in the compound of the formula (I), various non-toxic salts of 2-deoxy-2-[3S-(9-phenylnonanoyloxy)tetradecanoyl]amino-3-O-(9-phenylnonanoyl)-4-O-sulfo-D-glucopyranose of the formula (I-A) 
are disclosed in Japanese Kokai-koho Hei 6-41175 (EP 0226381).
However, there is no report that Glucopyranose derivatives of the present invention of the formula (I) or non-toxic salts thereof possess an activity of immunosuppression.
Energetic investigations have been carried out in order to make a compound having an activity of immunosuppression, e.g. IgE antibody production inhibition, and a high safety. The present inventors have found that Glucopyranose derivatives of the formula (I) or non-toxic salts thereof accomplished the present purpose.
The present invention relates to an immunosuppressant comprising Glucopyranose derivatives of the formula (I): 
wherein R is hydrogen, hydroxy or C1-4 alkoxy,
G is (1) 
in which R1 is a single bond or C2-20 oxycarbonylalkyl,
R2 is hydrogen or 
in which R8 is hydrogen, C1-7 alkyl, C1-7 alkoxy or halogen atoms, m is 1, 2 or 3;
R3 is C1-20 alkylene,
R4 is hydrogen or 
in which R9 is hydrogen, C1-7 alkyl, C1-7 alkoxy or halogen atoms, n is 1, 2 or 3; or
(2) 
in which Y is a single bond or C1-4 alkylene, p and q independently, is an integral of 6-12;
R5 is C2-20 oxycarbonylalkyl,
R6 is hydrogen or 
in which R8 and m are as hereinbefore defined; or
R5-R6 is 
in which Z is a single bond or C1-4 alkylene, r and s, independently, is an integral of 6-12;
R7 is hydrogen, methyl, hydroxymethyl or sulfoxymethyl;
with the proviso that (1) R2, R4 and R6 is not hydrogen at the same time,
(2) when R1 is C2-20 oxycarbonylalkyl, then R2 bonds to alkyl in R1,
(3) when R5 is C2-20 oxycarbonylalkyl, then R6 bonds to alkyl in R5;
or non-toxic salts thereof as active ingredient.